Abstract: Driving under the influence of drugs of abuse is an epidemic in the United States (U.S.) and has been identified as a priority area of research by the National Institute on Drug Abuse and the White House Office of National Drug Control Policy. This public health crisis is occurring on the background of a precipitous increase in the availability of marijuana across the U.S. However, it is not clear how smoked marijuana, particularly high potency products that are commonly used for medical and recreational purposes, affect driving performance. The aim of this study is to employ driving simulator methodology to characterize the impairing effects of several types of smoked marijuana in a tightly controlled laboratory setting by utilizing a randomized, placebo- controlled, outpatient, within-subject design, enrolling healthy, occasional marijuana smokers (n=24 completers, 12 M, 12 F). This study will examine smoked marijuana containing: 1) high concentrations of THC (20% THC, trace CBD), 2) high concentrations of CBD (10% CBD, trace THC), and 3) moderate concentrations of both CBD and THC (5% CBD, 10% THC), in comparison to inactive marijuana (0% THC, 0% CBD; negative control) and a dose of alcohol known to produce driving impairment (0.8 g/kg [which produces 0.08% breath alcohol concentration]; positive control), on performance in a driving simulator, a model that is predictive of on-road driving ability. Secondary aims include examining the abuse liability, cognitive/psychomotor performance, and physiological effects across the dose conditions; sex differences will also be explored. Overall, this study will use state-of the-art technology to yield new empirical data on drugged-driving performance following exposure to the most commonly abused illicit drug, marijuana. These findings will be highly relevant to public health and may directly inform recommendations for medical marijuana patients and public safety regulations.